BioMarin Pharmaceutical Inc (BMRN) 2023 Q3 法說會逐字稿

Hello, and welcome to the BioMarin Pharmaceutical Third Quarter 2023 Conference Call. (Operator Instructions)

您好，歡迎參加 BioMarin Pharmaceutical 2023 年第三季電話會議。 （操作員說明）

I will now turn the conference over to Traci McCarty, Head of Investor Relations. Please go ahead.

我現在將會議交給投資者關係主管 Traci McCarty。請繼續。

Thank you, Jan, and thank you all for joining us today. To remind you, this nonconfidential presentation contains forward-looking statements about the business prospects of BioMarin Pharmaceutical Inc., including expectations regarding BioMarin's financial performance, commercial products and potential future products in different areas of therapeutic research and development. Results may differ materially depending on the progress of BioMarin's product programs, actions of regulatory authorities, availability of capital, future actions in the pharmaceutical market and developments by competitors and those factors detailed in BioMarin's filings with the Securities and Exchange Commission, such as 10-Q, 10-K and 8-K reports.

謝謝你，Jan，也謝謝大家今天加入我們。提醒您，本非機密簡報包含有關 BioMarin Pharmaceutical Inc. 業務前景的前瞻性陳述，包括對 BioMarin 的財務業績、商業產品以及治療研究和開發不同領域的潛在未來產品的預期。結果可能會存在重大差異，具體取決於BioMarin 產品計劃的進展、監管機構的行動、資本的可用性、製藥市場的未來行動和競爭對手的發展以及BioMarin 向美國證券交易委員會提交的文件中詳細說明的因素，例如10- Q、10-K 和 8-K 報告。

On the call today from BioMarin management are JJ Bienaime, Chairman and Chief Executive Officer; Jeff Ajer, Executive Vice President, Chief Commercial Officer; Hank Fuchs, President, Worldwide Research and Development; Greg Guyer, Executive Vice President and Chief Technical Officer; and Brian Mueller, Executive Vice President and Chief Financial Officer. We do plan to end this call promptly at 2:30 p.m. Pacific Time, and we thank you for your understanding.

今天，BioMarin 管理層董事長兼首席執行官 JJ Bienaime 出席了電話會議； Jeff Ajer，執行副總裁兼商務長； Hank Fuchs，全球研發總裁； Greg Guyer，執行副總裁兼技術長；以及執行副總裁兼財務長布萊恩·穆勒 (Brian Mueller)。我們確實計劃在下午 2:30 立即結束本次通話。太平洋時間，感謝您的體諒。

I will now turn the call over to BioMarin's Chairman and CEO, JJ Bienaime.

我現在將電話轉給 BioMarin 董事長兼執行長 JJ Bienaime。

Thank you, Traci. Good afternoon, good morning, everybody. As you will have seen this afternoon, we announced that I have decided after over 18 years with BioMarin to retire as the Chairman and Chief Executive Officer effective December 1 of this year. And as many of you are aware, I recently actually turned 70, I cannot believe it myself. So I will not -- it will not be a surprise to you that succession planning has been underway with the Board over the past several years.

謝謝你，特蕾西。大家下午好，早安。正如您今天下午所看到的，我們宣布，在為 BioMarin 工作超過 18 年後，我決定從今年 12 月 1 日起退休，擔任董事長兼執行長。正如你們許多人所知，我最近已經 70 歲了，我自己都不敢相信。因此，我不會——您不會感到驚訝的是，過去幾年董事會一直在進行繼任計劃。

To these announcements and the appointment of Alexander Hardy to succeed me as CEO follows a thorough multiyear planning process. Together with the Board, we conducted a comprehensive search over the past year, and we are thrilled to have Alexander step into the role. As part of this transition, I will also step away from my position as Chairman of the Board of Directors. However, I'll continue to serve on the board until the 2024 Annual Meeting of Stockholders, and I will stay as a consultant to the company for the remainder of 2024. I look forward to working with Alexander and the Board during this period to ensure a smooth transition. I am pleased that our Lead Independent Director, Richard Meier, with Randy will be our new Chair of the Board.

這些公告以及亞歷山大哈迪 (Alexander Hardy) 接替我擔任執行長的任命遵循了全面的多年規劃流程。在過去的一年裡，我們與董事會一起進行了全面的搜尋，我們很高興亞歷山大接任這一職位。作為此次過渡的一部分，我也將辭去董事會主席職務。不過，我將繼續在董事會任職直至 2024 年股東年會，並且我將在 2024 年剩餘時間內繼續擔任公司顧問。我期待在此期間與 Alexander 和董事會合作，以確保平穩過渡。我很高興我們的首席獨立董事理查德·邁耶 (Richard Meier) 和蘭迪 (Randy) 將擔任我們的新任董事會主席。

When I joined the company in May 2005, we had just 1 marketed product and recorded about $26 million in annual revenues. Since then, our team has developed and commercialized 7 additional medicines, pioneered groundbreaking first and transform the lives of countless of patients.

當我 2005 年 5 月加入公司時，我們只有 1 個上市產品，年收入約 2,600 萬美元。從那時起，我們的團隊又開發了 7 種藥物並將其商業化，開創了突破性先河，改變了無數患者的生活。

BioMarin is now a profitable fully integrated industry leader and one of the most successful biotech company with annual revenues anticipated to be more than $2.4 billion this year and also expected to grow to close to $3 billion next year. BioMarin is extremely well positioned for substantial future growth and profitable rate. Our market cap has grown from around $300 million when I started as CEO to more than $15 billion today. Our stock price went from $6 when I joined a CEO 18 years ago to over $83 today at the close. So we have generated returns greater than the [XBI] index over the past 1 year, 3 years, 5 years and 18 years. BioMarin is now a profitable fully integrated industry leader with annual revenues of more than $2 billion and extremely well positioned for substantial future growth and profitability.

BioMarin 現在是一家盈利能力完全一體化的行業領導者，也是最成功的生物技術公司之一，今年的年收入預計將超過 24 億美元，明年也將增長到接近 30 億美元。 BioMarin 處於非常有利的位置，可以實現未來的大幅成長和獲利率。我們的市值已從我剛擔任執行長時的約 3 億美元成長到今天的超過 150 億美元。我們的股價從 18 年前我加入執行長時的 6 美元上漲到今天收盤時的 83 美元以上。因此，我們在過去 1 年、3 年、5 年和 18 年中創造了高於 [XBI] 指數的回報。 BioMarin 現在是一家盈利的、完全一體化的行業領導者，年收入超過 20 億美元，並且為未來的大幅增長和盈利能力做好了充分準備。

We have expanded from operating only in the United States when I started with the company with now at that time, 300 employees to setting our medicine in almost 80 countries around the world and more than 3,000 employees. As the company is poised for its next phase of growth with the recent introduction of Voxzogo and Roctavian, this is the ideal time to hand over the reins to the next leader.

我們的業務已經從我創辦公司時僅在美國開展業務，到現在擁有 300 名員工，發展到在全球近 80 個國家和 3,000 多名員工中開展業務。由於最近推出了 Voxzogo 和 Roctavian，該公司已為下一階段的成長做好了準備，因此現在是將權力移交給下一任領導者的理想時機。

In the search, the Board focused on finding a successor with experience, driving commercial growth and operational excellence, while at the same time, bringing a deep understanding of the science and a strong background in product development. We are confident that Alexander perfectly meets those criteria. As CEO of Genentech Alexander led the commercialization of 10 new products in therapeutic areas, including cancer and hemophilia.

在尋找過程中，董事會的重點是尋找一位經驗豐富、推動商業成長和卓越營運的繼任者，同時帶來對科學的深刻理解和強大的產品開發背景。我們相信亞歷山大完全符合這些標準。作為基因泰克首席執行官，亞歷山大領導了癌症和血友病等治療領域的 10 種新產品的商業化。

Serving as CEO of this industry-leading, innovative and impactful company over the past 18 years has been the highlight of my career. We have built an incredible organization with great potential to be further unlocked by Alexander and the team. While I will miss working with our talented and inspiring employees day in and day out, but I am confident that the company is well positioned for future success. So to those on the call today, thank you for your engagement and support over the years. I still also want to emphasize that I will still be involved with the company, and I will still be very involved with biotech in general, as you will find out in the future.

在過去 18 年裡，擔任這家領先業界、創新且具有影響力的公司的執行長是我職業生涯的亮點。我們已經建立了一個令人難以置信的組織，亞歷山大和團隊將進一步釋放巨大的潛力。雖然我會懷念與我們才華橫溢、鼓舞人心的員工日復一日地共事，但我相信公司已經為未來的成功做好了準備。因此，對於今天參加電話會議的各位，感謝你們多年來的參與和支持。我還想強調，我仍然會參與公司的工作，我仍然會積極參與生物技術的工作，正如你將來會發現的那樣。

So now let's turn back to the quarterly results. We are -- we were very pleased with the results in the third quarter, recording 15% total revenue growth compared to the third quarter last year and continued strong growth in earnings per share faster than revenue. These results were driven primarily by Voxzogo, which remains on track to become our first blockbuster product. We saw strong demand and uptake in the quarter, and we expect this trend to continue.

現在讓我們回到季度業績。我們對第三季的業績感到非常滿意，與去年第三季相比，總營收成長了 15%，每股盈餘持續強勁成長，成長快於營收。這些結果主要是由 Voxzogo 推動的，它有望成為我們的第一個重磅產品。我們在本季看到了強勁的需求和吸收，我們預計這種趨勢將持續下去。

In the third quarter, more than 300 additional children become -- began treatment with Voxzogo since the end of Q2 and additional strong growth is expected in Q4. As a result, today, we increased full year 2023 Voxzogo guidance to between $435 million and $455 million. With recent U.S. and European approvals of Voxzogo's age expansions, all ages in the U.S. and for children ages 4 months and older in Europe, over 1,000 additional children now have the opportunity to benefit from a longer Voxzogo treatment window. We are also pleased to share that based on increased sale finish manufacturing commitments, Voxzogo supply is planned to increase from '23 levels through the first and second quarter in 2024 and is expected to be fully unconstrained by midyear 2024.

第三季度，自第二季末以來，又有 300 多名兒童開始接受 Voxzogo 治療，預計第四季將出現強勁成長。因此，今天我們將 Voxzogo 2023 年全年指引提高至 4.35 億美元至 4.55 億美元之間。隨著美國和歐洲最近批准 Voxzogo 的年齡擴展，美國的所有年齡層以及歐洲 4 個月及以上的兒童，現在有超過 1,000 名兒童有機會從更長的 Voxzogo 治療窗口中受益。我們也很高興地告訴大家，基於增加的銷售成品製造承諾，Voxzogo 的供應量計劃在2024 年第一季和第二季從23 年的水平增加，並預計到2024 年年中將完全不受限制。

Moving now to Roctavian, where we have made tremendous progress building and connecting the network that will facilitate patient treatment, we're re-laying the groundwork for our patient access to Roctavian has taken time but has been an essential step to ensuring access and reimbursement. Well over 100 people have been tested for Roctavian AAV5 eligibility globally, which is the first step that a patient needs to do to determine if he can be treated with Roctavian. The seronegativity rate on the samples that were tested to date is approximately 70%. So 70% of the patient tested are eligible for Roctavian and they still need to have a liver scan, but most of the ineligibility comes from the AAV5 positivity. And we expect the testing momentum to continue as awareness and access increases.

現在轉到 Roctavian，我們在建立和連接網路以促進患者治療方面取得了巨大進展，我們正在為患者訪問 Roctavian 重新奠定基礎，雖然這需要時間，但這是確保訪問和報銷的重要一步。全球已有超過 100 人接受了 Roctavian AAV5 資格測試，這是患者確定是否可以接受 Roctavian 治療所需要做的第一步。迄今為止測試的樣本的血清陰性率約為 70%。因此，70% 的接受測試的患者符合 Roctavian 的資格，他們仍然需要進行肝臟掃描，但大多數不符合資格的原因是 AAV5 陽性。我們預計隨著意識和訪問的增加，測試勢頭將繼續下去。

While it has taken more time than anticipated to get global health care system wired to facilitate Roctavian treatment, we remain encouraged by the high level of interest and demand from patients, physicians, patient advocacy groups, hemophilia treatment centers and payers. In Europe, we have strong progress in the quarter and expect to have final German and Italian prices for Roctavian published by year-end. And in the U.S., significant momentum connecting the network to facilitate treatment is occurring. Jeff will provide more detail on launch progress and our updated expectations for Roctavian.

儘管為促進羅克塔維治療而建立全球醫療保健系統所花費的時間比預期要長，但患者、醫生、患者權益團體、血友病治療中心和付款人的高度興趣和需求仍然令我們感到鼓舞。在歐洲，我們本季取得了強勁進展，預計在年底前公佈 Roctavian 在德國和義大利的最終價格。在美國，連接網絡以促進治療的巨大勢頭正在出現。 Jeff 將提供有關發布進度以及我們對 Roctavian 的最新期望的更多詳細資訊。

Turning to BioMarin's record year-to-date revenues of nearly $1.8 billion in the first 9 months of the year. This represents 14% year-over-year growth, even with lower-than-expected contributions from Roctavian. These results underscore the strength of our business and the achievement of double-digit revenue growth and our profitability objectives as set out at the start of the year. The business is poised for strong growth in '24 and beyond. With Voxzogo continuing to exceed expectations and Roctavian access and reimbursement in place for a meaningful uptick next year, we believe BioMarin revenues are set up to approach $3 billion in 2024.

BioMarin 在今年前 9 個月創下了近 18 億美元的創紀錄收入。即使 Roctavian 的貢獻低於預期，這也意味著同比增長 14%。這些結果凸顯了我們業務的實力、實現了兩位數的收入成長以及我們年初制定的獲利目標。該業務預計在 24 年及以後實現強勁成長。隨著 Voxzogo 繼續超出預期，並且 Roctavian 的准入和報銷到位，明年將出現有意義的增長，我們相信 BioMarin 的收入將在 2024 年接近 30 億美元。

In summary, we have built an industry-leading company. The strategy to create a sustainably profitable and growing business that provides patients with innovative and essential medicine is coming to fruition. This future looks very bright for BioMarin, and I want to thank my colleagues for the tremendous collaboration and what we have built together. So thank you for continued support. I will now turn the call over to Jeff Ajer to discuss the commercial business update. Jeff?

總而言之，我們已經建立了一家領先業界的公司。創建可持續盈利和不斷增長的業務、為患者提供創新和基本藥物的策略即將取得成果。 BioMarin 的未來看起來非常光明，我要感謝我的同事們的巨大合作以及我們共同創造的成果。感謝您一直以來的支持。我現在將把電話轉給傑夫·阿傑 (Jeff Ajer)，討論商業業務的最新情況。傑夫？

Thank you, JJ, in so many ways. I'm very pleased with our commercial performance in the third quarter, resulting in $581 million in total revenues and representing 15% growth year-over-year, including Kuvan and 20% growth excluding Kuvan.

JJ，在很多方面謝謝你。我對我們第三季的商業表現非常滿意，總收入達到 5.81 億美元，年增 15%（包括 Kuvan），年增 20%（不包括 Kuvan）。

Turning to Voxzogo. As JJ mentioned, today we updated full year guidance to between $435 million and $455 million, representing approximately 165% year-over-year growth at the midpoint. Appreciating that the run rate for the fourth quarter and full year 2023 may seem conservative based on Voxzogo revenues of $123 million in the third quarter, we note the impact from supply constraints discussed last quarter continue to limit growth through the end of this year.

轉向沃克斯佐戈。正如 JJ 所提到的，今天我們將全年指引更新為 4.35 億美元至 4.55 億美元之間，相當於中點年增約 165%。基於 Voxzogo 第三季度 1.23 億美元的收入，第四季度和 2023 年全年的運行速度可能顯得保守，我們注意到上季度討論的供應限制的影響將繼續限制今年年底的增長。

While we continue to closely manage new patient growth and limit inventory stocking, we expect to fulfill smaller orders from various regions in Q4, while at the same time adding hundreds of new patients in the fourth quarter. As a reminder, new patient starts with Voxzogo in the fourth quarter will represent only a fraction of a full year revenue patient in 2023. Importantly, we expect approximately 2,600 patients to be receiving Voxzogo treatment by year-end 2023. Voxzogo supply is planned to increase from 2023 levels through the first and second quarters of 2024 and is expected to be fully unconstrained by midyear next year. These commitments will ensure that we have ample supply to exceed full year 2024 consensus currently at $624 million and support growth beyond 2024.

在我們繼續密切管理新患者成長並限制庫存的同時，我們預計將在第四季度履行來自各個地區的較小訂單，同時在第四季度增加數百名新患者。提醒一下，第四季度開始使用 Voxzogo 的新患者僅佔 2023 年全年患者收入的一小部分。重要的是，我們預計到 2023 年底將有約 2,600 名患者接受 Voxzogo 治療。Voxzogo 供應計劃到2024 年第一季和第二季度，產量將從2023 年的水準開始增加，預計到明年年中將完全不受限制。這些承諾將確保我們有充足的供應來超過 2024 年全年的共識（目前為 6.24 億美元），並支持 2024 年以後的成長。

At the end of the third quarter, more than 2,300 children with achondroplasia in 38 markets were being treated with Voxzogo. Uptake to date represents 12% penetration of indicated patients in BioMarin's commercial footprint, highlighting the significant growth potential remaining. With the opportunities now to treat up to an additional 1,000 children following the recent age expansion approvals in the U.S. and Europe, we look forward to the possibility of the youngest children in these regions benefiting from Voxzogo therapy.

截至第三季末，38 個市場的 2,300 多名軟骨發育不全兒童正在接受 Voxzogo 治療。迄今為止，BioMarin 商業足跡中指定患者的使用率已達 12%，凸顯了剩餘的巨大成長潛力。在美國和歐洲最近批准擴大年齡後，現在有機會治療另外 1,000 名兒童，我們期待這些地區最小的兒童有可能從 Voxzogo 療法中受益。

Turning now to Roctavian. We are pleased to share that the second commercial patient was treated today in Germany. As JJ highlighted, we continue to make progress connecting the network that will facilitate treatment. 2023 has turned out to be the year of building that network to ensure and support meaningful patient uptake in 2024.

現在轉向羅克塔維安。我們很高興地告訴大家，第二位商業患者今天在德國接受了治療。正如 JJ 所強調的那樣，我們在連接網絡方面不斷取得進展，這將有助於治療。 2023 年是建立此網路的一年，以確保和支持 2024 年有意義的患者吸收。

Starting with Europe, we have a tentative agreement with the German National Association of Statutory Health Insurance Funds, or GKV, on the final German price for Roctavian which we expect to be formalized and published by the end of the year. As we have said previously, we believe this important step given the unique treatment and reimbursement profile of Roctavian will open up the access bundle to treatment in Germany.

從歐洲開始，我們與德國國家法定健康保險基金協會 (GKV) 就 Roctavian 在德國的最終價格達成了初步協議，我們預計該價格將在今年年底正式確定並公佈。正如我們之前所說，鑑於 Roctavian 獨特的治療和報銷概況，我們相信這一重要步驟將為德國治療提供捆綁。

We are pleased to share that in Germany, 60 people are known to be eligible based on CDx testing for AAV5 antibodies. The vast majority of those are in follow-up for next steps. As expected, the seronegativity rate of about 70% is in line with our study results and consistent with expectations. We are also pleased to report that there are now 10 sites in Germany testing for eligibility. With a large pool of eligible patients and the final German price expected to be published soon, we are optimistic about patient uptake rates in 2024.

我們很高興地告訴大家，根據 AAV5 抗體的 CDx 檢測，在德國已知有 60 人符合資格。其中絕大多數正在跟進後續步驟。如預期的那樣，血清陰性率約為70%，這與我們的研究結果相符，符合預期。我們也很高興地報告，德國目前有 10 個站點進行資格測試。由於符合條件的患者數量眾多，而且德國最終價格預計很快就會公佈，我們對 2024 年的患者就診率持樂觀態度。

Important to note is that the first patient treated resulted in net revenue of approximately $800,000. Gross to net revenue adjustments going forward under the GKV agreement will be different than for the first patient reported, but our overall expectations are to maintain similar net revenue per patient in Germany, noting the impact of weight-based dosing and variable weight of patients.

值得注意的是，第一位接受治療的患者帶來的淨收入約為 80 萬美元。根據GKV 協議，未來的總收入與淨收入調整將與報告的第一位患者不同，但我們的總體預期是在德國保持每位患者類似的淨收入，並注意到基於體重的劑量和患者體重可變的影響。

In Italy, negotiations with the Italian Medicines Agency are going well, and we expect to have a final price published by year-end. Italy represents then our second major European market that has agreement on price and reimbursement, opening the door to Roctavian access likely in early 2024. We continue to work with the authorities in France and expect pricing negotiations to extend into 2024.

在義大利，與義大利藥品管理局的談判進展順利，我們預計在年底前公佈最終價格。義大利是我們在價格和報銷方面達成一致的第二個主要歐洲市場，可能會在 2024 年初為 Roctavian 進入市場打開大門。我們將繼續與法國當局合作，預計定價談判將延續到 2024 年。

It has taken several months in the U.S. following approval to align stakeholders and to facilitate first patients treated. In general terms, this is a result of that unique profile of onetime reimbursement and treatment with Roctavian. Navigating hospital administration and finance adds a level of complexity for hemophilia treatment centers or HTCs, leading to the final step of patient treatment with Roctavian. We expect that these administrative steps taken at the HTC level, while time consuming, are onetime events and essential to facilitate patient access going forward.

美國在獲得批准後花了幾個月的時間來協調利益相關者並為第一批患者提供治療。總的來說，這是 Roctavian 一次性報銷和治療的獨特特徵的結果。醫院管理和財務的管理增加了血友病治療中心或 HTC 的複雜性，導致患者接受 Roctavian 治療的最後一步。我們預計，在 HTC 層級採取的這些管理步驟雖然耗時，但卻是一次性事件，對於促進患者未來的訪問至關重要。

In short, the ground work completed in 2023 is expected to enable simplified access to Roctavian drive more and more AAV5 eligibility testing and giving us confidence in the prospects for 2024. However, with less than 2 months remaining in the year, and the holiday season beginning soon, we are lowering full year Roctavian 2023 guidance to less than $10 million.

簡而言之，預計2023 年完成的基礎工作將能夠簡化Roctavian 的訪問，推動越來越多的AAV5 資格測試，並使我們對2024 年的前景充滿信心。然而，距離今年剩下不到2 個月的時間，加上假期季節很快開始，我們將 Roctavian 2023 年全年指導下調至 1000 萬美元以下。

Moving now to our specific steps completed this quarter starting with the issuance of coverage policies across payers, both private and public. We are pleased to share that nearly 2/3 of all covered lives in the United States have been issued coverage policies to date representing approximately 205 million people. Importantly, the vast majority are in line with label or clinical trial criteria and are thus favorable in meeting expectations.

現在轉向我們本季完成的具體步驟，首先是向私人和公共付款人發布承保政策。我們很高興地告訴大家，迄今為止，美國近 2/3 的受保人已獲得保險保單，涵蓋約 2.05 億人。重要的是，絕大多數都符合標籤或臨床試驗標準，因此有利於滿足預期。

Additionally, we are encouraged by the rapid uptake of the outcomes-based warranty with signed warranties in place representing more than 95 million U.S. lives. We have also received notice that the J-code for Roctavian has been assigned effective January 1, 2024. The permanent J-code is expected to accelerate payer's prior authorization review process ultimately spending time to patient treatment. Taken together, these developments are a strong indication of the value to the U.S. health system places in a cost-effective onetime gene therapy.

此外，我們對基於結果的保固的迅速採用感到鼓舞，並簽署了代表超過 9500 萬美國人生命的保固。我們也收到通知，Roctavian 的 J 代碼已分配，並於 2024 年 1 月 1 日生效。永久 J 代碼預計將加快付款人的事先授權審查流程，最終將時間花在患者治療上。總而言之，這些進展有力地顯示了具有成本效益的一次性基因療法對美國衛生系統的價值。

We stated in our approval in Q2 earnings call, we expect it could take patients 2 to 5 months to complete the steps necessary before treatment with Roctavian. The commercial team has been hard at work implementing a number of tactics to prepare physicians, HTCs and patients for the opportunity to benefit from Roctavian. With respect to site readiness, HTC are being prepared and educated on how to administer Roctavian. We have targeted the largest and most capable HTCs for site readiness by year-end, a number of which have readiness plans before the end of this year.

我們在第二季財報電話會議上表示，我們預計患者可能需要 2 至 5 個月的時間才能完成接受 Roctavian 治療之前所需的步驟。商業團隊一直在努力實施多種策略，讓醫生、HTC 和患者有機會從 Roctavian 中受益。關於現場準備情況，HTC 正在就如何管理 Roctavian 進行準備和培訓。我們的目標是在年底前讓規模最大、能力最強的 HTC 做好現場準備，其中許多 HTC 已在今年年底前製定了準備計劃。

Increasing HTC and patient awareness in the U.S. was also an important focus in the quarter. A number of activities were conducted, including national HTC and patient webinars and the third annual Global Gene Therapy Scientific Summit sponsored by BioMarin. We are especially encouraged by the number of local patient advocacy groups which have been willing to host branded patient awareness programs for Roctavian. Medical eligibility, including CDx testing is underway. And as a result, the U.S. patient funnel is beginning to take shape giving us confidence in the prospects for treating patients going forward.

提高美國的 HTC 和患者意識也是本季的重要焦點。舉辦了一系列活動，包括全國 HTC 和患者網路研討會以及由 BioMarin 贊助的第三屆年度全球基因療法科學高峰會。我們尤其感到鼓舞的是，許多當地患者倡導團體願意為 Roctavian 舉辦品牌患者意識計畫。包括 CDx 測試在內的醫療資格正在進行中。因此，美國的患者漏斗開始形成，這讓我們對未來治療患者的前景充滿信心。

In conclusion, we are on track to achieve 2023 full year total revenue guidance driven by the strength of our inside product revenues and continued high demand for Voxzogo globally. Looking ahead, we believe the network built to facilitate treatment with Roctavian combined with our high expectations for Voxzogo and strong enzyme business will enable BioMarin to approach close to $3 billion in total revenues in 2024.

總而言之，在我們內部產品收入的實力和全球對 Voxzogo 持續高需求的推動下，我們預計將實現 2023 年全年總收入指引。展望未來，我們相信，為促進 Roctavian 治療而建立的網絡，加上我們對 Voxzogo 和強大酶業務的厚望，將使 BioMarin 的總收入在 2024 年接近近 30 億美元。

Thank you for your attention, and I will now turn the call over to Hank to provide an R&D update. Hank?

感謝您的關注，我現在將把電話轉給漢克，以提供研發最新資訊。漢克？

Thanks, Jeff. Thank you, JJ. The privilege has been ours. And thank you all for joining us today. We provided a thorough update on our earlier stage pipeline at R&D Day in September. So if you missed it, please find the full presentation on BioMarin's IR website.

謝謝，傑夫。謝謝你，傑傑。特權是我們的。感謝大家今天加入我們。我們在 9 月的研發日上提供了早期階段產品線的全面更新。因此，如果您錯過了，請在 BioMarin 的 IR 網站上找到完整的簡報。

Starting with Voxzogo in the quarter and shortly beyond, we received some important updates from global health authorities, resulting in expanded access to children -- younger children in both the U.S. where it is now approved in all age groups and in Europe for children 4 months of age and older. We're gratified that the youngest children now have the possibility of greater potential long-term benefits from treatment with Voxzogo. And I want to thank not just the usual clinical and regulatory teams at these finish line efforts, but also the extended BioMarin team of safety professionals, biometrics professionals, operations, pharmacology really the whole entire fully integrated team played a strong role in enabling this advancement in access of patients. So behalf of the families and children with achondroplasia, thank you all.

從本季度的Voxzogo 開始以及不久之後，我們收到了來自全球衛生當局的一些重要更新，從而擴大了兒童的使用範圍——在美國，該藥物現已被批准用於所有年齡段的兒童，在歐洲，該藥物可用於4 個月以下的兒童的年齡和年齡。我們很高興最小的孩子現在有可能從 Voxzogo 治療中獲得更大的潛在長期益處。我不僅要感謝通常的臨床和監管團隊在這些終點線所做的努力，還要感謝由安全專業人員、生物識別專業人員、營運、藥理學組成的BioMarin 擴展團隊，整個完全整合的團隊正在實現這一進步方面發揮了強大的作用方便患者接觸。我謹代表患有軟骨發育不全的家庭和兒童，感謝大家。

As mentioned last quarter, we have solidified our plans to begin the pivotal program using Voxzogo for the treatment of hypochondroplasia with a natural history arm of the study expected to begin this quarter. The pathogenesis and epidemiology are similar between achondroplasia and hypochondroplasia. Well, hypochondroplasia presents with a milder phenotype in some patients in terms of short stature disproportionate and clinical manifestations we plan to target the population with the most severe form of the disease, and therefore, the highest unmet need with high deficits beyond 3 standard deviations below the means.

正如上季度所提到的，我們已經鞏固了計劃，開始使用 Voxzogo 治療軟骨發育不全的關鍵項目，該研究的自然史部分預計將於本季度開始。軟骨發育不全和軟骨發育不全的發病機轉和流行病學相似。嗯，軟骨發育不良在一些患者中表現出較溫和的表型，包括身材矮小、不成比例和臨床表現，我們計劃針對患有最嚴重疾病形式的人群，因此，最高的未滿足需求與超過3 個標準差的高赤字辦法。

With alignment from FDA on a single registration-enabling 52-week randomized, double-blind, placebo-controlled study with the primary outcome of annualized growth velocity, we look forward to initiating the treatment arm of the study in 2024 following the natural history run-in portion.

根據 FDA 對一項為期 52 週的隨機、雙盲、安慰劑對照研究的統一註冊，其主要結果是年生長速度，我們期待在自然歷史運行之後於 2024 年啟動該研究的治療部分- 部分。

In addition, we plan to initiate 2 new clinical programs next year with Voxzogo, one in idiopathic or polygenic short stature and the other in defined genetic short stature conditions. We know that CNP is a pivotal physiologic stimulator of endochondral bone growth on the level of the growth plate. Further, human genetic studies of CNP and not FGFR3 demonstrate that even modest nudges and CNP signaling have a significant impact on final adult height.

此外，我們計劃明年用 Voxzogo 啟動 2 個新的臨床項目，一個針對特發性或多基因矮身材，另一個針對特定的遺傳性矮身材狀況。我們知道，CNP 是生長板水平軟骨內骨生長的關鍵生理刺激劑。此外，對 CNP 而不是 FGFR3 的人類遺傳學研究表明，即使是適度的推動和 CNP 訊號傳導也會對最終成年身高產生重大影響。

This supports our confidence that Voxzogo can deliver on the transformational improvement and growth across many forms of skeletal impairment while remaining -- while retaining the strong safety profile demonstrated in achondroplasia. For these reasons, we look forward to starting the clinical programs in these additional stature indications, in 2024.

這支持了我們的信心，即 Voxzogo 可以在多種形式的骨骼損傷中實現轉化性改善和生長，同時保持軟骨發育不全所表現出的強大安全性。基於這些原因，我們期待在 2024 年啟動這些額外身材適應症的臨床計畫。

Please take a look at the full R&D Day presentation, the latest update on our 7 portfolio candidates discussed in September, and we look forward to keeping you appraised as they progress through development. And thanks for your support, and I'll turn the call over to Brian to update financial results in the quarter, Brian?

請查看完整的研發日演示文稿，這是我們在 9 月討論的 7 個候選產品組合的最新更新，我們期待在它們的開發進展過程中不斷獲得您的評價。感謝您的支持，我會將電話轉給布萊恩，更新本季的財務業績，布萊恩？

Thank you, Hank, and thank you, JJ, as well. Please refer to today's press release summarizing our financial results for full details on the third quarter of 2023. Since JJ and Jeff spoke to our revenue performance for the quarter, and future revenue outlook, I will primarily focus on the remainder of our P&L and other key financial updates this quarter.

謝謝你，漢克，也謝謝你，JJ。請參閱今天總結我們財務業績的新聞稿，了解2023 年第三季度的完整詳細信息。由於JJ 和Jeff 談到了我們本季度的收入表現以及未來的收入前景，我將主要關注我們的損益表的其餘部分以及其他本季的重要財務更新。

As usual, all results will be available in our upcoming Form 10-Q, which we expect to file tomorrow. We are pleased with our year-to-date revenue growth of 14% and non-GAAP earnings per share growth of 33% and which well positions us to achieve our top and bottom line financial objectives in 2023, as indicated by our narrowed guidance provided today on total revenue and earnings per share. As underscored in today's guidance updates, we continue to expect double-digit revenue growth, coupled with meaningful P&L leverage with GAAP and non-GAAP earnings per share growth faster than revenue.

與往常一樣，所有結果都將在我們即將提交的 10-Q 表格中提供，預計明天提交。我們對今年迄今為止的收入增長 14% 和非 GAAP 每股收益增長 33% 感到滿意，這使我們能夠在 2023 年實現我們的營收和淨利潤目標，正如我們提供的縮小範圍指導所示今天的總收入和每股收益。正如今天的指導更新所強調的那樣，我們繼續預期兩位數的收入成長，加上有意義的損益槓桿，公認會計原則和非公認會計原則的每股盈餘成長速度快於收入。

Moving on to Q3 results. BioMarin's $581 million of total revenue in the third quarter of 2023 grew 15% compared to the third quarter of 2022 and 19% on a constant currency basis. Voxzogo's strong performance and healthy growth in the enzyme products marketed by BioMarin drove this result, with some partial offsets of lower Kuvan revenue due to continued generic competition and Aldurazyme timing of order fulfillment to Sanofi.

繼續看第三季的結果。 BioMarin 2023 年第三季的總營收為 5.81 億美元，較 2022 年第三季成長 15%，以固定匯率計算成長 19%。 Voxzogo 的強勁表​​現和 BioMarin 銷售的酵素產品的健康成長推動了這一結果，部分抵消了由於持續的仿製藥競爭和 Aldurazyme 向賽諾菲履行訂單的時間而導致的 Kuvan 收入下降。

The strength of our portfolio consisting of 8 commercial products allows us continued patients on the pioneering nature of the Roctavian launch, specifically the ability to maintain our original full year 2023 total revenue growth expectations which represents 16% of year-over-year growth at the midpoint and our implied Q4 2023 growth rate at the guidance midpoint of over 20%. We remain confident in the long-term prospects of Roctavian and its potential to drive growth in 2024.

我們由 8 種商業產品組成的產品組合的優勢使我們能夠繼續關注 Roctavian 推出的開拓性，特別是能夠維持我們最初的 2023 年全年總收入增長預期，即 2023 年同比增長 16%。中點，我們隱含的2023 年第四季成長率超過20% 的指導中點。我們對 Roctavian 的長期前景及其推動 2024 年成長的潛力充滿信心。

With respect to gross margin, Q3 2023 gross margin of 78.5% is an improvement of 1.6 percentage points as compared to the third quarter of 2022. R&D expense in Q3 2023 was $191 million, and SG&A expense was $224 million which combined together totaled $415 million and grew 11% versus last year. As compared to 15% revenue growth in the quarter, this aligns with our goal of growing operating expenses slower than revenue to deliver operating margin expansion for the full year. The increase in R&D and SG&A was primarily driven by the development of our early-stage pipeline and global commercial launch activities for Voxzogo and Roctavian. As we look ahead to the fourth quarter, we anticipate that total SG&A and R&D expense will be higher than Q3 on a dollar basis due to the same drivers.

毛利率方面，2023年第三季毛利率為78.5%，較2022年第三季增加1.6個百分點。2023年第三季研發費用為1.91億美元，SG&A費用為2.24億美元，合計4.15億美元與去年相比成長了11%。與本季 15% 的營收成長相比，這符合我們的目標，即營運支出成長速度慢於收入成長，以實現全年營運利潤率的擴張。研發和銷售、管理費用的成長主要是由我們早期產品線的開發以及 Voxzogo 和 Roctavian 的全球商業發布活動所推動的。展望第四季度，我們預計由於相同的驅動因素，以美元計算，SG&A 和研發費用總額將高於第三季。

Moving down the P&L. We continue to see an increase in interest income due to higher yields on our cash and investments. On tax expense for the quarter, I will note that we recognized tax expense at a lower effective rate during Q3 due to some discrete tax benefits during the quarter. This lower tax expense in Q3 will likely modestly benefit the full year tax as well, but we continue to project that our global annual effective tax rate will be in the 20% to 23% range over the next few years.

損益表向下移動。由於現金和投資收益率提高，我們的利息收入持續增加。關於本季的稅收費用，我要指出的是，由於本季出現了一些離散的稅收優惠，我們在第三季以較低的有效稅率確認了稅收費用。第三季較低的稅收支出可能也會適度有利於全年稅收，但我們繼續預測，未來幾年我們的全球年度有效稅率將在 20% 至 23% 的範圍內。

On the bottom line, we delivered on our commitment to profitability with $40 million of GAAP net income in Q3 '23, and $89.5 million of non-GAAP income. This level of profitability for Q3 and year-to-date gives us confidence to achieve our stated objective of sustained and growing profitability on a full year basis going forward. Year-to-date 2023 non-GAAP diluted earnings per share has increased 33% as compared to Q3 year-to-date last year. And today, we have reaffirmed our midpoint guidance for non-GAAP diluted earnings per share for the full year.

總而言之，我們兌現了盈利承諾，23 年第 3 季的 GAAP 淨利潤為 4,000 萬美元，非 GAAP 收入為 8,950 萬美元。第三季和年初至今的獲利水準讓我們有信心實現全年獲利能力持續成長的既定目標。 2023 年迄今的非公認會計原則攤薄每股收益與去年第三季相比成長了 33%。今天，我們重申了全年非公認會計原則攤薄每股收益的中點指引。

In closing, we are on track to meet our top line and bottom line objectives for 2023 and beyond with strong double-digit growth in both revenue and profitability. The continued success of Voxzogo, the momentum building for Roctavian and ongoing margin expansion efforts gives BioMarin a strong foundation to achieve our financial goal of being one of the industry leaders in revenue growth and margin expansion as we close 2023 and head into 2024.

最後，我們預計將實現 2023 年及以後的營收和利潤目標，營收和獲利能力均實現兩位數的強勁成長。 Voxzogo 的持續成功、Roctavian 的勢頭增強以及持續的利潤擴張努力為BioMarin 奠定了堅實的基礎，以實現我們的財務目標，即在2023 年結束並進入2024 年時成為收入增長和利潤擴張的行業領導者之一。

Thank you for your attention, and we will now open up the call for questions.

感謝您的關注，我們現在開始提問。

(Operator Instructions) Your first question comes from the line of Salveen Richter of Goldman Sachs.

（操作員說明）您的第一個問題來自高盛的 Salveen Richter。

JJ, it's been a pleasure working with you. Good luck on the next venture here. With regard to my question, you talked about the -- with Roctavian the HTC preparedness that's required. And then you also provided some context of 2 to 5 months to prepare patients for treatment. Can you just break that down for us like the time period needed for HTC the -- then kind of the payer dynamics that will play out the diagnostic aspect as well? And how demand is stacking up as you get a sense from physicians and lease centers right now?

JJ，很高興與你合作。祝你下次在這裡創業好運。關於我的問題，您與 Roctavian 談到了 HTC 所需的準備。然後您還提供了一些 2 到 5 個月的背景信息，以幫助患者做好治療準備。您能否為我們分解一下，例如 HTC 所需的時間段——然後那種付款人動態也將發揮診斷方面的作用？根據您目前從醫生和租賃中心了解到的情況，需求是如何增加的？

Salveen, I'll take a shot at that one. There's a lot of moving parts in this launch. There is the specific HTC dynamic which is not unique to Roctavian. So you may be getting some insights into how that's playing out in a parallel launch in the United States. The HTCs need to be prepared both for the administration of a onetime treatment with Roctavian, which includes handling a frozen product, a very high value it includes other dynamics like 340B discounting and pricing relative in some cases, to larger health care systems that may be a parent organization and have some capabilities that the HTC does or does not have.

Salveen，我會試試看。這次發布有很多活動部件。 HTC 的獨特動態並非 Roctavian 所獨有。因此，您可能會對在美國並行發布的情況有所了解。 HTC 需要為Roctavian 的一次性治療做好準備，其中包括處理冷凍產品，這是一個非常高的價值，它包括其他動態，例如340B 折扣和定價，在某些情況下相對於更大的醫療保健系統，這些系統可能是母組織，並且具有 HTC 擁有或不具備的一些功能。

So there's kind of those dynamics inside of the HTC. There's also the payer dynamics going on which you would expect anyway in the United States but in this case, the payer dynamics are complicated by the fact that gene therapies in a high-value onetime treatment are new and different. We've known and expected the payers will take some time to get their hands around that issue for years, and we've been preparing for that eventuality.

所以 HTC 內部就有這樣的動態。無論如何，在美國也存在著你所期望的付款人動態，但在這種情況下，由於高價值一次性治療中的基因療法是新的和不同的，付款人動態變得複雜。多年來，我們知道並預期付款人將需要一些時間來解決這個問題，我們一直在為這種可能性做好準備。

There's also patient awareness and interest in a highly competitive and very dynamic changing standard of care environment. There are physicians that have a number of options available to them. There's all those dynamics going on in parallel, and we're navigating all of those issues in parallel. Some are taking some time. I mentioned the payer dynamics specifically, what I believe is that the 2/3 of U.S. population with issued coverage policies 4 months after approval, I think is really encouraging and very, very fast. The uptake of the warranties, which is a brand-new thing for payers at the level that I described is very fast and very encouraging.

患者對競爭激烈且不斷變化的護理標準環境也有意識和興趣。有些醫生有多種選擇。所有這些動態都是並行發生的，我們正在並行解決所有這些問題。有些需要一些時間。我特別提到了付款人的動態，我認為，在批准後 4 個月內，2/3 的美國人口就獲得了承保政策，我認為這確實令人鼓舞，而且速度非常非常快。對於我所描述的水平的付款人來說，保固的接受度是一個全新的事情，速度非常快，非常令人鼓舞。

And we're seeing the patient funnel now starting to shape -- take shape in the United States. So I've been describing the patient funnel over the last year in Germany and the U.S. patient population is substantially larger than that of Germany. But early signals in the U.S. look like the taking shape of that patient funnel is going to have some similarities to what we've experienced in the United States, all of which gives me a great deal of confidence that as we finish up this year, hopefully, treat some patients in Q4 that we're really set up with payer approvals in Italy and Germany and the dynamics in the United States falling in place, all of which point to greater uptake in 2024. Thanks for the question.

我們看到患者漏斗現在開始形成—在美國形成。因此，我一直在描述去年德國的患者漏斗，而美國的患者人數遠多於德國。但美國的早期訊號看起來正在形成的患者漏斗將與我們在美國經歷的情況有一些相似之處，所有這些都給了我很大的信心，當我們今年結束時，希望在第四季度治療一些患者，我們確實已經在義大利和德國獲得了付款人批准，並且美國的動態正在落實到位，所有這些都表明2024 年會有更大的採用率。謝謝你的問題。

Your next question comes from the line of Geoff Meacham of Bank of America.

你的下一個問題來自美國銀行的傑夫‧米查姆。

Great. JJ, I also wanted to offer up congrats on the retirement. So not surprisingly, I have a few on Roctavian as well. So the first one is, I know you're not giving more detailed '24 guidance than the $3 billion in revenue. But at a high level, how would you characterize the Roctavian contribution? And the second question is, I guess, when you use Germany as a proxy, you have 60 patients that are pretty late in the onboarding process. It's been on the market officially for over a year. Is there what you characterize as a second wave or is the 60 mostly hit? I wasn't sure kind of if there's a bit of a ripple effect once you get formal reimbursement.

偉大的。 JJ，我也想對退休表示祝賀。所以毫不奇怪，我也有一些關於羅克塔維安的。所以第一個問題是，我知道你們不會提供比 30 億美元收入更詳細的 24 年指引。但從較高的層面來看，您如何評價羅克塔維安的貢獻？第二個問題是，我猜，當你使用德國作為代理人時，你有 60 名患者在入職過程中已經很晚了。它正式上市已有一年多了。是否存在您所描述的第二波浪潮，或者是 60 波主要受到衝擊？我不確定一旦獲得正式報銷是否會產生連鎖反應。

Thanks, Geoff, Brian here. I'll start with your first question. On the $3 billion, as you noted, haven't given the specifics behind that. We'll plan on doing that early next year like we typically would. But importantly, there's both continued growth in Voxzogo over '23 and a meaningful contribution from Roctavian. So we'll ask you to stay tuned for the details, but you understand what has been the typical growth trajectory for the mature enzyme products still growing healthily here, plus substantial growth in Voxzogo plus meaningful Roctavian contribution gets us to that approximately or approaching $3 billion.

謝謝傑夫、布萊恩。我將從你的第一個問題開始。正如你所指出的，關於 30 億美元，尚未給出背後的具體細節。我們將計劃在明年初像往常一樣這樣做。但重要的是，Voxzogo 在 23 年來持續成長，而 Roctavian 也做出了有意義的貢獻。因此，我們要求您繼續關注詳細信息，但您了解仍在健康增長的成熟酶產品的典型增長軌跡，加上Voxzogo 的大幅增長，加上Roctavian 的有意義的貢獻，使我們的收入大約或接近3美元十億。

As usual, we will give more detailed guidance when we report Q4 in February of next year.

像往常一樣，我們將在明年 2 月報告第四季時提供更詳細的指導。

And I think great question about the 60 AAV5 eligible patients that have yet to be treated in Germany. Actually the pace of CDx testing in Germany slowed down over the summer. That's probably a reflection both of the general slowdown in August, in particular, in Germany, and also a reflection that, as I've noted previously, our earlier plan to treat patients in the free pricing period while we are negotiating with TKV wasn't paying out the way we had hoped it would.

我認為關於 60 名尚未在德國接受治療的 AAV5 合格患者的問題很大。事實上，德國 CDx 測試的步伐在整個夏天放緩了。這可能既反映了 8 月的整體經濟放緩，尤其是在德國，也反映了，正如我之前指出的，我們之前在與 TKV 談判時在免費定價期內治療患者的計劃並不理想。並沒有按照我們希望的方式支付。

So we know the HTCs were slowing down in Germany waiting for the GKB process to be finished. My perception is a pickup following the end of the summer in CDx activity and lining up patients to be treated in Germany is both reflective of, one, getting past the summer and, two, an expectation that these HTCs know essentially that we've come to conclusion on price. They're just waiting for that price to be published, so they can move ahead with patient treatment.

因此，我們知道 HTC 在德國的速度正在放緩，等待 GKB 流程完成。我的看法是，夏季結束後 CDx 活動有所回升，患者排隊前往德國接受治療，這既反映了第一，已經度過了夏季，第二，期望這些 HTC 基本上知道我們已經來了得出價格結論。他們只是在等待價格公佈，以便繼續進行患者治療。

And while we're on the subject of Germany, which the physicians in Germany and the data on other launches would bear out, Germany moved slow for adoption of new hemophilia options. Having 60 patients in Germany that are AAV5 eligible on a population of base -- adjusted basis in the United States would equate to about 240 to 250 patients. So just benchmarking what may be the possibilities in the U.S.

雖然我們談論的是德國，德國的醫生和其他發布的數據都證實了這一點，但德國在採用新的血友病治療方案方面進展緩慢。德國有 60 名符合 AAV5 資格的患者，根據調整後的美國人群，相當於約 240 至 250 名患者。因此，只需對美國的可能性進行基準測試即可。

Your next question comes from the line of Phil Nadeau of Cowen.

你的下一個問題來自考恩的菲爾·納多（Phil Nadeau）。

JJ, let me add our congratulations on a very successful tenure and your retirement from BioMarin. Again, a couple of follow-ups on Roctavian, specifically on patient demand. In the last earnings call, you mentioned that patient consent forms had been trending well and BioMarin was happy with the rate that they had started to come in. Any update on outpatient consent forms are trending? And is there any visibility on when the first U.S. patients could be treated? That's question one.

JJ，請容許我對您在 BioMarin 的成功任職和退休表示祝賀。同樣，對羅克塔維安進行了一些後續行動，特別是針對患者需求。在上次財報電話會議中，您提到患者同意書的趨勢良好，BioMarin 對它們開始進入的速度感到滿意。門診同意書的趨勢有任何更新嗎？是否可以預見第一批美國患者何時可以接受治療？這是問題一。

And then question two, in terms of the institutional challenges, we've had some physicians mentioned things like training staff, beds need to be set up, equipment needs to be ordered. Are those challenges at the HTCs, and if so, is there anything BioMarin can do to remove those bottlenecks?

然後是第二個問題，就體制挑戰而言，我們有一些醫生提到了諸如培訓人員、需要設置床位、需要訂購設備之類的事情。 HTC 面臨這些挑戰嗎？如果是，BioMarin 可以做些什麼來消除這些瓶頸嗎？

Thank you for the question, Phil. So let me start with the second point first. The institutional challenges. In the prepared remarks, I addressed HTC site readiness and some of the elements of that, that I think are onetime events that won't be recurring. The types of things that you just mentioned, I would say, generally are captured in that HTC site readiness and some of the institutional things that they're doing to get ready for Roctavian treatment in particular and taking a little bit of time, which should be resolved and facilitate patients to move expeditiously through those types of things going forward.

謝謝你的提問，菲爾。那我先從第二點開始。體制挑戰。在準備好的演講中，我談到了 HTC 網站準備以及其中的一些要素，我認為這些都是一次性事件，不會重複發生。我想說，您剛才提到的事情類型通常體現在 HTC 現場準備情況以及他們正在做的一些機構事情，特別是為 Roctavian 治療做好準備，並且需要一點時間，這應該得到解決並幫助患者迅速完成這些類型的事情。

In terms of patient demand in the United States, we're not disclosing patient-level detail in the United States, but we're continuing to see, as I noted, that patient funnel buildup in the U.S. and I'm qualitatively encouraged by what we're seeing so far. In the U.S., we have this hub operation. And in prior launches, all of the patients moved through our hub essentially first before they move through the next step towards treatment.

就美國的患者需求而言，我們沒有披露美國患者層面的詳細信息，但正如我所指出的，我們繼續看到美國患者漏斗的積累，我從質量上受到鼓舞到目前為止我們所看到的。在美國，我們有這個樞紐業務。在先前的發布中，所有患者基本上首先經過我們的中心，然後再進行下一步治療。

Given the nature of the HTCs and their capabilities and the fact that they operate in this multi-sponsor environment, we've been seeing patients come into our hub maybe later in the process and not at the very beginning of the process. So this is a little bit of a different dynamic for us. We're getting our hands around that one. But yes, encouraged by the patient demand that we're seeing in the United States and the patient funnel building up.

考慮到 HTC 的性質及其能力以及它們在多贊助商環境中運作的事實，我們看到患者可能在流程的後期而不是在流程的一開始就進入我們的中心。所以這對我們來說有點不同。我們正在著手解決這個問題。但是，是的，受到我們在美國看到的患者需求和患者漏斗的建立的鼓舞。

In addition to the funnel building up, I mean, it is possible, I think that was your question, can we treat some U.S. patients by year end? I would say, yes, it is possible. We have 3 U.S. patients who have now cleared all Roctavian screens for treatment, like the AAV5 liver scan, liver health and all that. So the timing of their treatment isn't guaranteed in '23, but they have completed all eligibility testing for treatment. So it will very likely occur in the not-too-distant future.

除了漏斗的建立之外，我的意思是，有可能，我認為這是你的問題，我們可以在年底前治療一些美國患者嗎？我想說，是的，這是可能的。我們有 3 名美國患者現已透過所有 Roctavian 篩檢進行治療，例如 AAV5 肝臟掃描、肝臟健康等等。因此，他們的治療時間不能保證在 23 年，但他們已經完成了所有治療資格測試。因此，它很可能會在不遠的將來發生。

Your next question comes from the line of Robyn Karnauskas of Trust.

您的下一個問題來自 Trust 的 Robyn Karnauskas。

Great. I have 3 quick questions. Number one, JJ, you have mentored so many people on The Street, so appreciative. Is Hank retiring too, because then we will have a panic attack. So like -- would you like an announcement on that call? Is Traci getting a promotion? That's our first question.

偉大的。我有 3 個簡單的問題。第一，JJ，你在華爾街指導了很多人，非常感激。漢克也退休了嗎，因為那樣我們就會陷入恐慌。那麼，您想了解有關該電話會議的公告嗎？特蕾西升職了嗎？這是我們的第一個問題。

The second question would be Roctavian. There was such a focus and you misguided this year on the outcome of what you could achieve. Do you think in 2024, you can do better? And then I think on Voxzogo, I mean that similarly from our analyst meeting is like the big takeaway. So how do you think about letting analysts understand the opportunity there and the time lines for that. And I'll go back to Traci's promotion, is Hank leaving. I'll leave it at that.

第二個問題是羅克塔維安。今年你對自己能夠實現的目標的關注如此集中，但卻誤導了你。您認為 2024 年可以做得更好嗎？然後我認為在 Voxzogo 上，我的意思是我們的分析師會議上的類似內容就像是一個大收穫。那麼，您如何考慮讓分析師了解那裡的機會及其時間表。我會回到特雷西的晉升，漢克離開。我就這樣吧。

Thank you, Robyn. I mean -- I think there was a previous question from -- I think, from Salveen and we had a detailed answer from analyst -- from Geoff. Indeed, it has taken longer than we anticipated to get the -- to connect the patient with the treatment centers, to get the whole system wired. So again, big picture, when you have such a big ticket item like Roctavian, $3 million WACC, it attracts a lot of -- people -- so essentially, it's a big pie that attracts a lot of players that really don't get involved in the decision-making because they all kind of want a piece of the action. Just so Jeff mentioned of 340B though.

謝謝你，羅賓。我的意思是——我認為之前有一個問題是來自薩爾文——我想是來自薩爾文，我們從分析師——傑夫那裡得到了詳細的答案。事實上，將患者與治療中心連接起來、連接整個系統所花費的時間比我們預期的要長。再說一次，從大局來看，當你擁有像Roctavian 這樣的大門票項目，WACC 為300 萬美元時，它會吸引很多人，所以本質上，這是一個大餡餅，吸引了很多真正不了解的玩家參與決策，因為他們都想從行動中分一杯羹。正如傑夫提到的 340B 一樣。

I mean all -- basically all hemophilia patients in the U.S. statutory wise are 340B patients. It was like 20% 340B discount a $3 million WACC drug, exactly about $600,000. As you can understand many people get interested in that pie, and they want a slice of it, which just slows things down, but eventually long term, it's actually good news and will be taken care of.

我的意思是，基本上美國法定的所有血友病患者都是 340B 患者。這就像 300 萬美元 WACC 藥物的 20% 340B 折扣，大約是 60 萬美元。你可以理解，很多人對這塊餡餅很感興趣，他們想要分一杯羹，這只會減慢速度，但最終從長遠來看，這實際上是個好消息，並且會得到照顧。

So the fact that the takeoff has been delayed, we and to us at BioMarin has no impact on the future potential of this drug. It's taking longer than planned. It took longer -- sorry, the first time we got a product approved in Europe before the U.S. and Roctavian got approved in Germany and based on our previous experiences we thought we could be able to treat some patients during the free pricing period in Germany, which is slowly disappearing. Didn't happen then.

因此，我們和 BioMarin 的起飛推遲這一事實對該藥物的未來潛力沒有影響。花費的時間比計畫的要長。花了更長的時間——抱歉，我們第一次在美國獲得產品批准，而 Roctavian 在德國獲得批准，根據我們之前的經驗，我們認為我們可以在德國的免費定價期間治療一些患者，正在慢慢消失。那時沒有發生。

We are basically very, very close to a final deal with the German authority. So which generally takes about 12 to 13 months of -- in this respect. We're not that far behind versus the European approval. So again, we believe Roctavian has great potential. We believe Roctavian would be a significant contributor in 2024 and beyond.

我們基本上非常非常接近與德國當局達成最終協議。因此，在這方面，通常需要大約 12 到 13 個月的時間。與歐洲的認可相比，我們並沒有落後太多。因此，我們再次相信 Roctavian 具有巨大的潛力。我們相信 Roctavian 將在 2024 年及以後做出重要貢獻。

Obviously, not as much as Voxzogo, which is turning into a very, very large drug based on our Q3 results particularly Q4 and as the fact that thanks to the efforts of our drug supply team, all the constraints in terms of packaging that we had and sealed finish that we had this year are starting to go away, and will be much more substantial. We will have much more substantial capacity in '23 in Q1 and Q2 and then free of all capacity constraints by the middle of the year. So hope that answers your question and I'll get back to you regarding Traci.

顯然，沒有Voxzogo 那麼多，根據我們第三季度的結果，特別是第四季度的結果，Voxzogo 正在變成一種非常非常大的藥物，而且由於我們藥物供應團隊的努力，我們在包裝方面的所有限制都得到了解決。我們今年的密封飾面開始消失，並且會更加堅固。我們將在 23 年第一季和第二季擁有更多的產能，然後在年中擺脫所有產能限制。希望這能回答您的問題，我會回覆您有關特雷西的問題。

Your next question comes from the line of Joseph Schwartz of Leerink Partners.

您的下一個問題來自 Leerink Partners 的 Joseph Schwartz。

Great. And best wishes to JJ. That's really the end of an era. So I guess I was wondering if you can help us understand what kinds of initiatives you've undertaken to address the administrative delays and site readiness issues and what kind of success have you had where you have implemented these things? And what initiatives do you have left to implement still to support Roctavian's growth? Any more color there would be very helpful.

偉大的。並向JJ致以最美好的祝愿。這確實是一個時代的結束。所以我想我想知道您是否可以幫助我們了解您為解決管理延遲和網站準備問題採取了哪些舉措以及您在實施這些措施方面取得了哪些成功？為了支持 Roctavian 的發展，您還需要實施哪些措施？任何更多的顏色都會非常有幫助。

Thanks, Joe, for your question. I would characterize the answer to that as less specific initiatives and more just the nuts and bolts and mechanics of selling, providing scientific support to HTCs, physicians, patient advocacy groups, including local chapter events. All the things that help them through those little steps and lots of little decisions, including the big decision of affirmatively making the decision to treat.

謝謝喬的提問。我將這個問題的答案描述為不太具體的舉措，而更多的是銷售的具體細節和機制，為 HTC、醫生、患者倡導團體（包括當地分會活動）提供科學支持。所有幫助他們完成這些小步驟和許多小決定的事情，包括積極做出治療決定的重大決定。

And as Hank and I have discussed just this week, we're really focused on those small tactical on-the-ground elements with our teams to just keep those things moving through the various little challenges that are popping up. So it's more about dealing with those little things, getting to the other side of them, many of which are onetime events and less about introducing new initiatives.

正如漢克和我本週剛剛討論過的那樣，我們真正專注於與我們的團隊一起進行的那些小型戰術要素，以確保這些事情能夠應對突然出現的各種小挑戰。因此，更多的是處理這些小事情，解決它們的另一面，其中許多都是一次性事件，而不是引入新的舉措。

And if I may add to it regarding Germany, again, in Europe, patients don't pay for drugs. They don't -- they don't pay either for doctor's visit. So they don't know the price of the drug. But, one, so the key thing in Europe is to have official government reimbursement for your drug. That's about to happen in Germany and Italy. We basically, as we have said, we have an agreement on the price in Germany already.

如果我可以補充德國的情況，那麼在歐洲，病人不支付藥物費用。他們不——他們也不支付看醫生的費用。所以他們不知道這種藥的價格。但是，第一，在歐洲，關鍵是讓政府對你的藥物進行官方報銷。德國和義大利即將發生這種情況。正如我們所說，我們基本上已經就德國的價格達成了協議。

Now we need to have this price published, which will occur over the next few weeks. Once that happens, there is no barrier whatsoever left in Germany for the 60 patients that are 85 negative in Germany, it's very likely that the vast majority of them will be treated. Obviously, most of them next year because there are so few weeks left in this year because of the holiday season coming up pretty soon and the fact that the price probably won't be published for another 3 or 4 weeks.

現在我們需要公佈這個價格，這將在接下來的幾週內發生。一旦發生這種情況，德國境內的 60 名 85 陰性患者就不再有任何障礙，他們中的絕大多數很可能會接受治療。顯然，大多數都是明年，因為今年只剩下幾週了，因為假期即將到來，而且價格可能還要再過三四周才會公佈。

Your next question comes from the line of Chris Raymond of Piper Sandler.

您的下一個問題來自 Piper Sandler 的 Chris Raymond。

And congrats from us to JJ, and sorry to see you leave JJ and really enjoyed working with you all these years. I've got 2 question, maybe 1 a commercial one, maybe for Jeff, and then 1 for Hank, if that's okay. So maybe just on Voxzogo, Jeff, on that supply constraint issue, maybe could you talk a little bit about the triage process that you've instituted with new patient starts. I guess I'm just kind of wondering what kind of retention programs do you have in place for those new patients who want to be on therapy, but can't? And can you give us a sense of that number now? And where you expect it to grow to when you get back up to supply mid next year and start to treat those patients?

我們向 JJ 表示祝賀，很遺憾看到你離開 JJ，這些年來和你一起工作真的很愉快。我有 2 個問題，也許 1 是一個商業問題，也許是針對 Jeff 的，然後是 1 個問題是針對 Hank 的，如果可以的話。因此，傑夫，也許就 Voxzogo 而言，關於供應限制問題，也許您可以談談您對新患者啟動的分類流程。我想我只是想知道對於那些想要接受治療但不能接受治療的新患者，你們有什麼樣的保留計劃？現在您可以讓我們了解一下這個數字嗎？當你明年年中恢復供應並開始治療這些患者時，你預期它會成長到什麼程度？

And then maybe on the R&D side, Hank, just noticing back at your R&D Day, which was just in September, I think your cardiomyopathy programs I think 293 was supposed to have its initial data proof of concept in 2025 and I think 365 was the year after. It looks like those have been pushed a year. It's only been a few weeks since your R&D Day. Maybe is there a sense of what's happening there?

然後也許在研發方面，漢克，剛剛注意到你們的研發日，就在 9 月份，我認為你們的心肌病變計畫我認為 293 應該在 2025 年擁有其初始數據概念證明，我認為 365 是一年後。看起來這些已經延後一年了。距離您的研發日才過去幾週。也許你能感覺到那裡正在發生什麼事？

Thanks, Chris. So let's start with the Voxzogo supply constraint issue, and I'll ask Greg and Brian to jump in if they think I'm missing any here. But qualitatively, what I can tell you is, by the time we were looking at our patient demand and the resulting unit demand forecast, the very beginning of this year we anticipated that we would be getting to a point during the course of 2023 that we would not be able to satisfy all of the patient demand that we saw springing up in all of our commercial footprint.

謝謝，克里斯。那麼，讓我們從 Voxzogo 供應限制問題開始，如果 Greg 和 Brian 認為我在這裡遺漏了任何問題，我會請他們介入。但從質量上來說，我可以告訴你的是，當我們研究患者需求和由此產生的單位需求預測時，今年年初，我們預計我們將在 2023 年達到這樣的程度：將無法滿足我們在所有商業足跡中看到的所有患者需求。

A reminder that we're active now in 38 markets. So our objective was twofold during the course of the year. The first was to ensure or do our best to ensure that if we were starting patients on Voxzogo therapy in any of those markets that we could assure the supply continuity behind those specific patients and that we would minimize or eliminate the risk that patients starting therapy would have to go off therapy for either a very short or a prolonged time, which required a lot of forward planning. And a reminder, you hear a lot about the different dynamics of markets.

提醒您，我們目前活躍於 38 個市場。因此，我們這一年的目標是雙重的。首先是確保或盡最大努力確保，如果我們在任何這些市場中開始對患者進行 Voxzogo 治療，我們可以確保這些特定患者背後的供應連續性，並且我們將最大限度地減少或消除患者開始治療的風險必須在很短或很長的時間內停止治療，這需要大量的前瞻性計劃。提醒一下，您會聽到很多關於市場不同動態的資訊。

The different markets look very different. So having a 38 market footprint to be projecting into -- projecting those patient demands looking at our labeled product supply going out 6 to 9 months forward was a pretty dynamic situation to manage, but getting on top of that early allowed us to say in certain markets we're going to delay our entry into that market because we can't be assured of keeping patients on therapy once we start them, but also having a forward-looking date that would be able to communicate and say, look, if we can't get into this market on May of this year, for example, with an increasing supply -- still supply constrained, but supply increasing when could we project that market to come online for patients to be treated.

不同的市場看起來非常不同。因此，要預測38 個市場足跡——透過未來6 到9 個月的標籤產品供應來預測這些患者的需求，這是一個需要管理的動態情況，但儘早掌握這一情況使我們能夠在某些情況下說我們將推遲進入該市場，因為一旦我們開始治療，我們就不能保證讓患者繼續接受治療，但也有一個前瞻性的日期，能夠溝通並說，看，如果我們例如，今年5 月無法進入這個市場，供應不斷增加——供應仍然有限，但供應增加，我們何時可以預測該市場上線以供患者接受治療。

Those are the kind of dynamics that we were working through. And as you can tell by the different quarterly results in our remarks during the year, we've now kind of reached that point where there are patients in certain markets that we are attempting to not get started on therapy because we can't guarantee supply. And there are markets that we have earmarked for the future to open up and begin treating patients because we couldn't guarantee the continuity of supply for earlier starts. Maybe I'll pause there and look at Brian or Greg for additional comments.

這些就是我們正在經歷的動態。正如您在我們今年的演講中不同的季度結果中可以看出的那樣，我們現在已經達到了這樣的程度：某些市場上的患者我們試圖不開始治療，因為我們無法保證供應。我們已指定未來開放一些市場並開始治療患者，因為我們無法保證早期啟動的供應連續性。也許我會在這裡暫停一下，看看 Brian 或 Greg 以獲得更多評論。

Yes, Chris, this is Greg. I'll just add. So the way you should think about it is, and Jeff stated that for the end -- for the fourth quarter, we kind of will add 300 new patients, as you said. What you have to think about is we have done a lot of work since we were last on the call with you. And first quarter is less constrained. Second quarter is almost close to not constrained. And by midyear, we'll have no constraints.

是的，克里斯，這是格雷格。我就補充一下。所以你應該這樣考慮，傑夫表示，在第四季末，我們將增加 300 名新患者，正如你所說。您必須考慮的是，自從上次與您通話以來，我們已經做了很多工作。第一季受到的限制較少。第二季幾乎接近不受限制。到年中，我們將不再受到任何限制。

So it is getting better by the day. So it's not like some event happens in midyear. It gets us to totally unconstrained. We're going to be building inventory and building supply and able to support more and more of those patients. There is a significant uplift in patients in the first half of next year that we'll be able to support and then by midyear we'll be fully unconstrained for all those markets, all those patients. So think of it as a taper over time that we will start to go after those patients as opposed to some event that will consume all those patients in midyear, if that helps.

所以情況一天比一天好。所以這不像年中發生什麼事件。它讓我們完全不受約束。我們將建立庫存和供應，並能夠為越來越多的患者提供支援。明年上半年，我們將能夠支持的患者數量顯著增加，然後到年中，我們將完全不受所有這些市場、所有患者的限制。因此，隨著時間的推移，我們將開始關注這些患者，而不是在年中發生一些會消耗所有患者的事件（如果有幫助的話）。

And then, Chris, I just want to address your question about certain earlier-stage programs shifting. They haven't. As part of our ongoing efforts to streamline communications, we're going to be updating the Street when we have clinical proof of concept. So those dates, just the points in time when we're communicating updates have changed, but none of the actual advances have changed.

然後，克里斯，我只想回答你關於某些早期專案轉移的問題。他們沒有。作為我們簡化溝通的持續努力的一部分，當我們獲得臨床概念驗證時，我們將更新《華爾街日報》。所以這些日期，只是我們溝通更新的時間點發生了變化，但實際的進展都沒有改變。

The next question comes from the line of Paul Matteis of Stifel.

下一個問題來自 Stifel 的 Paul Matteis。

Great. And I'll add my congrats to JJ as well. I appreciate the question. I was curious, when you were undertaking the CEO search and succession planning over the past couple of years, what were the 2 to 3 key things that you were prioritizing?

偉大的。我也會向 JJ 表示祝賀。我很欣賞這個問題。我很好奇，過去幾年您在進行 CEO 搜尋和繼任計畫時，您優先考慮的 2 到 3 件關鍵事情是什麼？

And as you were thinking on selecting new leadership, how important was it that a new CEO would really stay the course in BioMarin's core strategy over the past few years? Or I guess what I'm kind of trying to say is as we think forward, what are the chances here that Alexander Hardy does actually enact material changes over the next 6 to 12 months and BioMarin in certain ways could look differently?

當您考慮選擇新的領導層時，新任執行長在過去幾年中真正堅持 BioMarin 的核心策略有多重要？或者我想我想說的是，當我們展望未來時，Alexander Hardy 在未來 6 到 12 個月內真正實施重大變革的可能性有多大，而 BioMarin 在某些方面可能會有所不同？

Yes. So let me try to answer your question. So we've done a pretty comprehensive search mainly over the past year or so that accelerated about a few months ago. And we had several very good candidates and the Board thought that Alexander was probably the best candidate. As you know, he served as CEO of Genentech since 2019.

是的。那麼讓我試著回答你的問題。因此，我們主要在過去一年左右進行了相當全面的搜索，大約幾個月前加速了搜索。我們有幾個非常好的候選人，董事會認為亞歷山大可能是最好的候選人。如您所知，他自 2019 年起擔任基因泰克執行長。

Over there, he was responsible for the company's $25 billion a year business and leading 13,500 employees. So we believe that he has demonstrated ability to deliver growth, which is -- what is -- continues to be needed at BioMarin. He steered Genentech through the loss of exclusivity of 3 major drugs during that time that together accounted for 40% of the company's revenues in 2019 and he returned the portfolio to strong growth by the end of 2022.

在那裡，他負責公司每年 250 億美元的業務並領導 13,500 名員工。因此，我們相信他已經展示了實現成長的能力，而這正是 BioMarin 繼續需要的。在此期間，他帶領基因泰克度過了 3 種主要藥物失去獨家經營權的時期，這三種藥物合計佔該公司 2019 年收入的 40%，並在 2022 年底使該組合恢復強勁增長。

So we believe that he has the ability to grow -- to continue to grow our commercial business pretty successfully. We understand from reference checks that he is a very good leader. And he's been evolving and working in competitive markets, of course, a range of therapeutic areas, including hemophilia, as you might have noticed. And he has overseen the launch of 10 new molecular entities during his time as CEO of Genentech. So he has a strong background and understanding in drug development and science.

所以我們相信他有能力成長——繼續相當成功地發展我們的商業業務。我們從背景調查中了解到他是一位非常優秀的領導者。當然，正如您可能已經注意到的那樣，他一直在競爭激烈的市場中不斷發展和工作，包括血友病在內的一系列治療領域。在擔任 Genentech 執行長期間，他監督了 10 個新分子實體的上市。因此，他在藥物開發和科學方面擁有深厚的背景和理解。

So he was -- Alexander hasn't been hard to make some major changes within BioMarin, but he is going to assess the situation and will determine what needs to be changed, if anything. But I think we all look forward to working with Alexander.

所以他 - Alexander 並不難在 BioMarin 內部做出一些重大改變，但他將評估情況並確定需要改變的內容（如果有的話）。但我認為我們都期待與亞歷山大合作。

Your next question comes from the line of Akash Tewari of Jefferies.

您的下一個問題來自 Jefferies 的 Akash Tewari。

This is Ivy on for Akash. And JJ congrats on the retirement. The forward questions. So I guess, for 2024, I know you haven't given any product specific details for Roctavian. What will be the cadence of new patients to add next year for both U.S. and ex U.S.? Because consultants right now has [350 million] contribution from Roctavian which looks quite high compared to the below 10 guidance you have for this year. So what do you think needs to happen to hit that target? Or is it like a fair target to say?

這是阿卡什的常春藤。 JJ 恭喜他退休。前向問題。所以我想，對於 2024 年，我知道你們還沒有給出 Roctavian 的任何產品具體細節。明年美國和美國以外地區新增患者的節奏是怎麼樣的？因為顧問現在有 Roctavian 的 [3.5 億] 貢獻，與今年的以下 10 項指導相比，這看起來相當高。那麼您認為要實現該目標需要做些什麼？或者說這是一個公平的目標嗎？

And secondly, I think for your mid-decade Voxzogo of around $4 billion to $5 billion, are there any updated thoughts to that target? And if you were to break down this $5 billion by product, how much of it is from Voxzogo? And how much of it is from Roctavian?

其次，我認為對於 Voxzogo 的 40 億至 50 億美元左右的十年中期目標，對此目標有什麼更新的想法嗎？如果按產品細分這 50 億美元，其中有多少是來自 Voxzogo？其中有多少是來自羅克塔維安？

I'll start with the big picture revenue question. This is Brian, and Jeff can maybe touch on the cadence briefly. So I touched on this a little bit in Jeff's question earlier. The key takeaway from the approaching $3 billion of revenue expectation for 2024 is that Roctavian is expected to come online globally, mostly Germany and U.S. And that the challenges and delays that we discussed for 2023 in the context of 2024, we expect to be timing.

我將從整體收入問題開始。我是布萊恩，傑夫或許可以簡單談談節奏。所以我之前在傑夫的問題中談到了這一點。 2024 年收入預期接近 30 億美元，主要收穫是 Roctavian 預計將在全球範圍內上線，主要是在德國和美國，而且我們在 2024 年背景下討論的 2023 年挑戰和延遲預計將在 2024 年實現。

Jeff and JJ touched on the German price dynamics. We've got the patient funnel filling up with what we believe to be the final gate which is concluding the price and getting the publication in the national register. That should open up that pool of patients for 2024.

Jeff 和 JJ 談到了德國的價格動態。我們已經讓患者漏斗充滿了我們認為是最終的大門，即敲定價格並在國家登記冊上發佈出版物。這應該會在 2024 年開放該患者庫。

In the U.S., Jeff, on a couple of the answers has talked about these dynamics that are coming together, positive momentum. But that's why we use the terminology network to bring all of those pieces together, patient-physician interest, site readiness, contracting and reimbursement, they all need to come together to have patients come online. That's taken longer in 2023, but we expect to be making significant progress over the next few months where we'll start to see those patients come online in '24. So the key takeaway from that $3 billion is that there is a meaningful piece of Roctavian there, which is a bridge from where we're at in '23.

在美國，傑夫在幾個答案中談到了這些正在聚集的動態，積極的勢頭。但這就是為什麼我們使用術語網路將所有這些部分整合在一起，患者與醫生的興趣、站點準備、合約和報銷，它們都需要結合在一起才能讓患者上網。到 2023 年，這需要更長的時間，但我們預計在接下來的幾個月中將取得重大進展，我們將開始看到這些患者在 2024 年上線。因此，這 30 億美元的關鍵收穫是，其中有 Roctavian 的一個有意義的部分，它是我們 23 年所處位置的一座橋樑。

And then briefly, no changes to the $4 billion to $5 billion. Obviously, we need to continue to monitor and execute on both Voxzogo and Roctavian. We've commented previously that, that $4 billion to $5 billion is roughly made up of half of the base business with continued growth and half of Roctavian and Voxzogo.

然後簡單地說，40 億至 50 億美元沒有變化。顯然，我們需要繼續對 Voxzogo 和 Roctavian 進行監控和執行。我們之前評論過，40 億至 50 億美元大致由持續成長的基礎業務的一半以及 Roctavian 和 Voxzogo 的一半組成。

But I think we refer you to some comments that -- answers to questions that we had previously on the call that -- to answer your question because they were asked earlier. Sorry, we're running out of time.

但我認為我們建議您參考一些評論——回答我們之前在電話會議中提出的問題——回答您的問題，因為之前有人問過這些問題。抱歉，我們的時間不多了。

Your next question comes from the line of Jessica Fye of JPMorgan.

你的下一個問題來自摩根大通的傑西卡·菲伊。

JJ, best wishes for your retirement. Recognizing what you're doing to manage supply with Voxzogo, can you just talk qualitatively about the geographic mix of Voxzogo sales? And which regions or countries have the most growth left in front of them in achondroplasia?

JJ，祝您退休順利。在認識到您正在為管理 Voxzogo 的供應所做的工作之後，您能否定性地談談 Voxzogo 銷售的地理組合？哪些地區或國家軟骨發育不全的成長速度最快？

Yes, I don't think that we're disclosing market-level detail, Jess, but overall, I mentioned that we're 12% patient penetrated of the indicated patient population, which includes the 4 months and up in Europe and from birth essentially in the United States. There is some variability in uptake. I think I have mentioned previously that early rapid uptake in places like Germany and Japan leave them at a relatively higher penetration rate so far without ceilings, but a higher rate in other places, importantly, like the United States, which just had a huge expansion of the patient population open to us in that patient population. Very young patients having the strongest value proposition for treatment opens up a lot of penetration room in the United States, for example. Probably too much detail to get into for other markets.

是的，我不認為我們正在披露市場層面的細節，Jess，但總的來說，我提到我們的患者滲透率達到了指定患者群體的12%，其中包括歐洲4 個月及以上的患者以及從出生起的患者基本上是在美國。吸收存在一定的差異。我想我之前已經提到過，德國和日本等地的早期快速普及使它們迄今為止具有相對較高的滲透率，沒有上限，但其他地方的滲透率更高，重要的是，像美國，剛剛經歷了巨大的擴張向我們開放的患者群體中的患者群體。例如，具有最強治療價值主張的非常年輕的患者在美國開闢了一個很大的滲透空間。對於其他市場來說，可能需要了解太多細節。

And your last question comes from the line of Ellie Merle of UBS.

你的最後一個問題來自瑞銀集團的埃莉梅爾。

Just in terms of the Voxzogo expansion studies, just from a disease biology perspective, how should we think about the potential mechanistically for CNP to expand into other indications relative to FGFR inhibitors. I guess, are there indications where you think biology might make more sense for CMP and not FGFR or vice versa? Or where you think CNP is particularly likely to be active?

就Voxzogo擴展研究而言，僅從疾病生物學的角度來看，我們應該如何從機制上考慮CNP擴展至與FGFR抑制劑相關的其他適應症的潛力。我想，是否有跡象表明您認為生物學可能對 CMP 而不是 FGFR 更有意義，反之亦然？或者您認為 CNP 在哪裡特別有可能活躍？

Ellie, thanks for asking the question so that I could both say unequivocally to Robyn's earlier question, I am here and very committed to BioMarin. And probably for exactly this reason, I think that when you look at the genetics of statural impairments and our group has actually published quite nicely on this that gain-on-function mutations in CNP confer a height benefit, loss-of-function mutations, convey short stature across a polygenic background. That, I think, is very strong evidence that CNP is going to be a dominant regulator of bone growth.

Ellie，感謝您提出這個問題，這樣我就可以明確地回答 Robyn 之前的問題，我在這裡並且非常致力於 BioMarin。可能正是因為這個原因，我認為當你研究身材缺陷的遺傳學時，我們的小組實際上已經發表了相當好的文章，CNP 中的功能獲得性突變會帶來身高優勢，功能喪失性突變，在多基因背景下表達身材矮小。我認為，這是非常有力的證據，表明 CNP 將成為骨骼生長的主要調節劑。

Interestingly, you can find loss of function or like gain of function variance in FGFR3. When they are associated with stature, they're also associated with profound other abnormalities. So that's why we think that the CNP access is going to be the perfect target for improving stature across a wide range of both genetic and polygenic indications and why FGFR3 approaches are primarily going to be limited to FGFR3 abnormalities. You can get a lot of height benefit, nudging the CNP access safely. You have to hit the FGF access quite hard in non-FGF indications and probably to toxic effect. At least that's based on human genetic data. So thanks for the question. We're very excited about that future.

有趣的是，您可以在 FGFR3 中發現功能損失或類似功能增益的變化。當它們與身材相關時，它們也與其他嚴重的異常有關。因此，我們認為 CNP 接觸將成為在廣泛的遺傳和多基因適應症中改善身材的完美目標，也是為什麼 FGFR3 方法主要僅限於 FGFR3 異常的原因。您可以獲得很多身高優勢，安全地推動 CNP 通道。在非 FGF 適應症中，您必須非常努力地利用 FGF 通路，並且可能會產生毒性作用。至少這是基於人類遺傳數據的。謝謝你的提問。我們對這個未來感到非常興奮。

There are no further questions at this time. I will now turn the call over to JJ Bienaime, Chairman and CEO.

目前沒有其他問題。我現在會把電話轉給董事長兼執行長 JJ Bienaime。

Thank you, operator, and thank you all for joining us today. We are pleased with our results this quarter and our prospects ahead. BioMarin is now a profitable, fully integrated industry leader with annual revenues well over $2 billion and is extremely well positioned for substantial future growth and profitability.

謝謝運營商，也謝謝大家今天加入我們。我們對本季的業績和未來的前景感到滿意。 BioMarin 現在是一家盈利的、完全一體化的行業領導者，年收入遠超過 20 億美元，並且為未來的大幅增長和盈利能力做好了充分準備。

Thank you for your continued support, and have a good afternoon or evening.

感謝您一直以來的支持，祝您下午或晚上愉快。

This concludes today's conference call. You may now disconnect.

今天的電話會議到此結束。您現在可以斷開連線。